title: Enteric-coated cysteamine for the treatment of paediatric non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver disease in children. Hepatic fat accumulation and oxidative stress contribute to its pathogenesis. Cysteamine bitartrate readily traverses cellular membranes and is a potent antioxidant.
  
  
  OBJECTIVE
  To evaluate the safety and efficacy of enteric-coated (EC) cysteamine in children with NAFLD.
  
  
  METHODS
  Children, aged ≥10 y, meeting screening criteria with biopsy-proven NAFLD and serum ALT ≥60 IU/L, received twice-daily EC-cysteamine for 24 weeks. Monthly ALT, AST, body mass index (BMI) and gastrointestinal symptom scores were measured. Subjects with >50% reduction or normalisation of ALT achieved the primary endpoint.
  
  
  RESULTS
  Of the 13 children enrolled (mean age 14.0 years), 11 completed EC-cysteamine therapy (mean dose 15.2 mg/kg/day) and were included in the final analysis. For these 11 subjects, the mean ALT levels at baseline and 24 weeks were 120.2 and 55 IU/L respectively (P = 0.002), and the AST levels were 60 and 36 IU/L respectively (P = 0.007). The primary endpoint was reached in 7 and normalisation (≤40 IU/L) of ALT in 5. After 24 week therapy, mean adiponectin levels increased (P = 0.009) and CK-18 fragment levels decreased (P = 0.013), insulin levels remained unchanged (P = 0.99). Mean leptin levels were decreased in responders (P = 0.044). Mean BMI was 34.5 at baseline and 34.2 kg/m(2) after treatment (P = 0.35). Mean symptom scores at baseline (1.1) and at 24 weeks (0.7) were similar. No major adverse events were reported.
  
  
  CONCLUSIONS
  Enteric-coated cysteamine reduces ALT and AST levels in children with NAFLD without reduction in body mass index. Further studies will evaluate optimal cysteamine therapeutic dose and effect on liver histology in NAFLD (Clinicaltrials.gov protocol ID: 07-1699).
authors.affiliation: Department of Pediatrics, University of California, Rady Children's Hospital, San Diego, USA.
authors.forename: R
authors.initials: R
authors.lastname: Dohil
authors.forename: S
authors.initials: S
authors.lastname: Schmeltzer
authors.forename: B L
authors.initials: BL
authors.lastname: Cabrera
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Durelle
authors.forename: K B
authors.initials: KB
authors.lastname: Duke
authors.forename: J B
authors.initials: JB
authors.lastname: Schwimmer
authors.forename: J E
authors.initials: JE
authors.lastname: Lavine
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000293:Adolescent; D000975:Antioxidants / Q000627:therapeutic use; D015992:Body Mass Index; D001835:Body Weight; D002648:Child; D003543:Cysteamine / Q000008:administration & dosage*; D005234:Fatty Liver / Q000188:drug therapy; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D018384:Oxidative Stress; D010865:Pilot Projects; D013608:Tablets, Enteric-Coated; D000637:Transaminases / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D052242:Adiponectin; D000975:Antioxidants; D013608:Tablets, Enteric-Coated; D003543:Cysteamine; D000637:Transaminases